Stroke

A stroke occurs when the blood supply to part of the brain is suddenly interrupted due to the presence of a blood clot (ischemic stroke) or when a blood vessel in the brain bursts, spilling blood into the spaces surrounding brain cells (hemorrhagic stroke). When blood flow to the brain stops, brain cells no longer receive oxygen and nutrients from the blood and die. Sudden bleeding in or around the brain can also cause brain cells to die. This results in temporary or permanent neurologic impairment. Ischemic stroke, also known as cerebral infarction, accounts for 80 - 85% of all strokes, while hemorrhagic stroke accounts for the other 15 - 20%. Prior to a stroke, some people suffer transient ischemic attacks (TIAs), mini-strokes that generally last only 5 - 20 minutes but can linger for up to 24 hours before the symptoms go away completely. Many times, a TIA is a warning of an impending stroke. An estimated 700,000 people in the United States suffer a stroke each year, making this one of the most serious of all health problems. Half of stroke sufferers are left disabled, with many undergoing years of rehabilitation.

Symptoms of a stroke depend on which area of the brain is affected and, in turn, what functions in the body that area controls. Many of the warning signs of a possible stroke (like a TIA) and symptoms of an actual stroke are the same. If any of these symptoms occur, you should seek medical attention right away and start appropriate treatment as quickly as possible. The sooner treatment begins, the more likely it is that brain function will be preserved.

Symptoms and warning signs include:

Sudden weakness or numbness of the face, arm, and leg on one side of the body

Sudden loss of vision or dimmed vision, particularly in one eye

Loss of speech, or trouble talking or understanding speech

Sudden, severe headaches with no apparent cause

Unexplained dizziness, unsteadiness, or sudden falls, especially if accompanied by any of the previous symptoms

Women are more likely to report nontraditional symptoms of stroke and, in particular, altered mental states.

A clot (embolus) forms in a part of the body other than the brain, travels through blood vessels, and becomes wedged in a brain artery.

A blood clot (thrombus) forms in a brain artery and stays attached to the artery wall until it grows large enough to block blood flow.

Hemorrhagic stroke results from the following causes:

A bleeding aneurysm -- a weak or thin spot on an artery wall that, over time, has stretched or ballooned out under pressure from blood flow. The wall ruptures and blood spills into the space surrounding brain cells.

Artery walls lose their elasticity and become brittle and thin, prone to cracking.

Arteriovenous malformation (AVM) -- a tangle of defective blood vessels and capillaries within the brain that have thin walls that can rupture.

Free radical damage may make someone susceptible to stroke and other brain disorders. Free radicals are waste products created when the body turns food into energy (metabolism). Even though they are created naturally by normal metabolic processes (called oxidation), free radicals cause harmful chemical reactions that can damage cells in the body. There are also many environmental sources of free radicals, such as ultraviolet rays, radiation, and toxic chemicals in cigarette smoke, car exhaust, and pesticides. Anyone can have a stroke, but certain factors place you at higher risk. You can't change some factors that increase the risk of stroke, while you can change others linked to lifestyle.

Anybody can have a stroke, but certain factors place you at higher risk. Some factors that increase the risk of stroke cannot be changed, while others are linked to lifestyle factors, and thus are under your control.

Risk factors that cannot be changed:

Age -- The older a person gets, the greater the risk of stroke.

Sex -- Men are 30% more likely to have a stroke than women. But after menopause, a woman's risk of stroke rises significantly.

Family history -- Having a parent, grandparent, or sibling who has had a stroke, puts you at greater risk yourself.

Race -- African-Americans have a greater risk of stroke than Caucasians. This is related to an increased risk of high blood pressure, obesity, and diabetes in African-Americans.

Heart attack – If you have had a heart attack in the past, you are more likely to have a stroke than someone who has not had a heart attack.

A history of migraine headaches -- Recent studies indicate that people with migraines may be at higher risk for ischemic stroke.

A prior stroke -- If you have had a stroke, you are at increased risk for another.

Sickle cell anemia -- People with this condition are at risk for stroke at a younger age.

Berry aneurysms -- Some people are born with small, sac-like areas within the wall of an artery in the brain. They occur most often at the junctures of vessels at the base of the brain. Berry aneurysms may rupture without warning, causing bleeding within the brain.

Risk factors that can be changed with medical treatment:

High blood pressure -- High blood pressure has no symptoms, so regular blood pressure checks are important. The condition can be easily and successfully controlled with medication.

High blood cholesterol levels -- Studies have shown that lowering cholesterol levels by changing your lifestyle and taking medication can reduce the risk of stroke by as much as 30%. Keeping cholesterol low can reduce the risk of blood clots and plaque buildup within the walls of arteries in the brain.

TIAs, or "mini-strokes" -- A surprising number of people ignore the symptoms of TIAs, which are warning signs that a stroke may be imminent. In fact, 50% of people who have had a TIA suffer a stroke within one year. It is very important to seek medical attention for these symptoms because if you have had a TIA, there are definite steps you can take to help prevent a major stroke. Doctors prescribe blood thinners such as aspirin, warfarin (Coumadin), or other drugs to prevent blood clots if you have had a TIA.

Cardiovascular disease -- Certain disorders of the heart or blood vessels, such as atherosclerosis (plaque buildup in artery walls) and atrial fibrillation (an abnormal heart rhythm), can produce blood clots that may break loose and travel to the brain. These conditions are also treated with blood thinners to reduce risk of stroke.

Diabetes -- People with diabetes are more at risk. It is important to note that type 2 diabetes (often called adult onset) is highly influenced by certain lifestyle factors, particularly diet and excess weight.

Blood clotting disorders -- People who form blood clots more easily, called hypercoagulable conditions, are at greater risk for stroke. Hypercoagulable states are also treated with blood thinners such as warfarin (Coumadin) in order to try to prevent stroke and other complications.

Sleep apnea -- People with sleep apnea have 3 - 6 times the risk of stroke compared to people who do not have this disorder. This condition, defined as cessation of breathing many times throughout the night, is generally treatable by losing weight and using a special device called a CPAP machine.

Risk factors that can change through lifestyle modifications:

Cigarette smoking -- Cigarette smoking has been linked to heart attacks, strokes, artery disease in the legs, and lung cancer. Nicotine raises blood pressure, carbon monoxide reduces the amount of oxygen the blood can carry to the brain, and cigarette smoke makes the blood thicker and more likely to clot. It is never too late to give up smoking.

Smoking and birth control pills -- Research shows that smoking and taking birth control pills significantly increases a woman's risk for stroke. Together, they can cause blood clots to form. Women who take birth control pills should not smoke.

Drinking large amounts of alcohol -- Frequent intoxication can make a person more likely to experience bleeding in the brain. Also, alcohol in large amounts can raise blood pressure.

Obesity -- Being overweight increases your risk of having a stroke, along with other health problems.

Poor diet -- A diet high in fat and sugar can cause conditions within the body -- such as obesity, type 2 diabetes, and high cholesterol -- that contribute to a greater risk of stroke.

Stress -- Ongoing stress can raise blood pressure. Plus, not dealing well with stress can contribute to unhealthy habits such as smoking and overeating. Finding healthy ways to handle stress is important.

Other factors that may put you at increased risk for stroke include pregnancy, infection or inflammation, gum disease, and high homocysteine levels. Homocysteine is an amino acid that rises in the body if you have low levels of vitamins B6, B12, B9 (folic acid), and betaine.

If you or someone you know experiences symptoms associated with stroke, call 911 or your local emergency number immediately. There are effective therapies for stroke that must be administered at a hospital within the first 3 hours after stroke symptoms appear. At the hospital, a health care provider will make a diagnosis and guide you in determining which treatment or combination of therapies will work best for you. The health care provider will do a complete neurological exam and run a battery of tests, such as blood tests, an electrocardiogram, and a test to measure the severity of the stroke. Imaging techniques -- such as CT scans, magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) -- may be used to reveal the cause of the stroke and pinpoint blockages or reveal malformations.

The best way to prevent stroke is to reduce your risk factors and take control of your own health:

If you smoke, stop smoking -- many excellent smoking cessation programs are available; your health care provider can advise you about tools to use, such as the nicotine patch, as well as exercise and other behavioral modifications.

Keep your weight within normal limits.

Get a moderate amount of exercise, preferably 5 days a week.

Eat a diet that is rich in fruits and vegetables. Green leafy vegetables may be particularly important, as well as whole grains, nuts (especially walnuts), and fish.

If you have heart disease or an abnormal heart rhythm, work with your doctor to treat it. Certain types of problems with the heart and blood vessels, such as atherosclerosis and atrial fibrillation, can cause blood clots to form. These clots can travel through the bloodstream and block an artery in the brain, causing a stroke (or can block a blood vessel in the heart and cause a heart attack).

If you have high blood pressure, take your medication regularly.

Lower your cholesterol level if it is elevated -- some people can do this by modifying their diet; others need to take medication. Lowering cholesterol levels has been proven to reduce the risk of stroke.

If you have diabetes, keep it under good control.

Know the warning signs of TIAs and strokes, and get help right away if you experience them.

Medications for prevention

Certain medications have been shown to reduce the risk of stroke. These drugs, which aim to prevent the formation of dangerous blood clots, fall under two major categories:

Antiplatelet agents -- These include aspirin and stronger prescription drugs like ticlopidine (Ticlid) and clopidogrel (Plavix). In one study, aspirin therapy reduced the risk of cardiovascular events, including stroke, by 21%. These drugs help keep tiny blood cells called "platelets" from clumping together in the bloodstream. When a blood vessel is damaged or injured, platelets will migrate to the area to begin a healing process. However, large numbers of platelets can clump together and form a clot that plugs up an artery. Antiplatelet agents help prevent this clumping.

Anticoagulants -- These drugs also prevent clots, but are much stronger than antiplatelet agents. Common anticoagulants are warfarin (Coumadin) and heparin (generally given at the hospital through injection into a vein).

A stroke is a medical emergency, regardless of whether it is a major stroke or a short-lasting TIA.

A person suffering symptoms consistent with a stroke should be taken immediately to a hospital emergency department.

The ability to quickly pinpoint the type of stroke is critically important in treatment decisions. A stroke caused by a blocked artery is treated in an entirely different way than a stroke caused by bleeding within the brain.

The key to survival and recovery is prompt medical treatment.

Lifestyle

Rehabilitation -- learning certain skills that you might have lost is crucial following a stroke and can consist of one or more of the following:

Psychological/psychiatric therapy -- To help relieve some mental and emotional stresses (such as depression) that often accompany a stroke. These feelings may be due to the location of the brain damage itself or may be a reaction to the stroke.

In addition, learning yoga may help you recover after a stroke, even months later. If you have had a stroke and are considering yoga, talk to your doctor first. Then, find a qualified teacher in your area who has worked a lot with stroke victims. This is very important because there are certain yoga postures that you should not do if you have high blood pressure, narrowed carotid arteries (the main arteries in your neck supplying blood to the brain), or history of stroke. Check with your physical therapist for a referral.

Medications

If the stroke is caused by a blockage in an artery, medications called thrombolytics can be used. The only drug in this class approved by the Food and Drug Administration (FDA) for treatment of stroke is tissue plasminogen activator (tPA). Popularly referred to as clot busting, this medication has been used for years to treat heart attacks and only more recently has been used as part of the treatment of stroke.

Not all hospitals have the ability to give tPA to people having a stroke. Before this drug can be given, doctors must be certain that the stroke is the result of a blockage in the artery, not due to bleeding from an artery. This is determined through imaging procedures such as a computed tomography (CT) scan or magnetic resonance imaging (MRI). But not all hospitals have around-the-clock imaging services. If the stroke is due to bleeding, this powerful blood thinner can worsen the hemorrhage.

If tPA cannot be used (for example, too much time has passed since the stroke symptoms began), your doctor may consider a less potent blood thinner called heparin.

Once the acute phase of the stroke has resolved, other less potent blood thinners called antiplatelet agents (such as aspirin and ticlopidine) or anticoagulants (such as warfarin) may be used to prevent future strokes due to blood clots (See "Preventing Care").

If a stroke is caused by bleeding, medication (such as mannitol) can reduce swelling of brain tissue.

Following the acute treatment of a stroke, while in recovery, medications to control risk factors for stroke like high blood pressure and high cholesterol will be started or adjusted if you are already taking. Daily aspirin is also recommended for those who have had a stroke or a TIA.

Surgery and Other Procedures

If the stroke or TIA is caused by a blockage, a procedure called carotid endarterectomy can be used to remove the buildup of plaque from inside the effected carotid artery, one of the major vessels supplying blood to the head and neck.

This surgical procedure is best for those who have had symptoms and have a blockage of 70% or more of one of their carotid arteries. If the narrowing of the vessel is less than 50%, medication (not surgery) is the most appropriate treatment to prevent future strokes.

Unfortunately, carotid endarterectomy may actually cause a stroke. Therefore, the risks and benefits of this procedure must be carefully weighed with your doctor.

If the stroke is caused by bleeding, an artery within the brain can sometimes be "clipped" to prevent further bleeding. Emergency surgery for a bleeding stroke may involve locating and surgically evacuating (removing) blood that has pooled in the brain tissue (called a hematoma). A brain specialist, called a neurosurgeon, will determine if this procedure is appropriate or not.

Interventional radiologists, if this specialized service is available at your hospital, may be trained to perform carotid angioplasty. This procedure begins with carotid angiography, as described earlier, to locate the blockage in this main artery supplying blood to the brain. Once located, a tiny balloon is threaded up to the blocked area and then inflated to break up the clot or plaque responsible for the narrowing in the vessel. The specialist may leave a wire mesh (stent) inside the vessel to keep it open. This procedure is quite risky, however, and may even cause a stroke.

If an aneurysm is present but has not bled, your doctor will discuss the possibility of removing it surgically. The decision is based primarily on the size of the aneurysm.

Nutrition and Dietary Supplements

Stroke should be treated by conventional medicine. If complementary and alternative therapies are used, they should bu used only under the supervsion of a health care provider.

Potentially beneficial nutritional supplements include the following:

Alpha-lipoic acid. Alpha-lipoic acid works together with other antioxidants, such as vitamins C and E. It is important for growth, helps to prevent cell damage, and helps the body rid itself of harmful substances. Because alpha-lipoic acid can pass easily into the brain, it has protective effects on brain and nerve tissue and shows promise as a treatment for stroke and other brain disorders involving free radical damage. Animals treated with alpha-lipoic acid, for example, suffered less brain damage and had a four times greater survival rate after a stroke than the animals who did not receive this supplement, especially when alpha-lipoic acid is combined with vitamin E. While animal studies are encouraging, more research is needed to understand whether this benefit applies to people as well.

Calcium. In a population based study (one in which large groups of people are followed over time), women who take in more calcium, both through the diet and supplements, were less likely to have a stroke over a 14 year period. More research is needed to fully assess the strength of the connection between calcium and risk of stroke.

Folic Acid, Vitamin B6, Vitamin B12, and Betaine. Many clinical studies indicate that patients with elevated levels of the amino acid homocysteine are as much as 2.5 times more likely to suffer from a stroke than those with normal levels. Homocysteine levels are strongly influenced by dietary factors, particularly vitamin B9 (folic acid), vitamin B6, vitamin B12, and betaine. These substances help break down homocysteine in the body. Some studies have even shown that healthy individuals who consume higher amounts of folic acid and vitamin B6 are less likely to develop atherosclerosis than those who consume lower amounts of these substances. One recent study found that loweing of homocysteine with folic acid and vitamins B6 and B12 reduced the overall risk of stroke, but not stroke severity or disability. Despite these findings, the American Heart Association (AHA) reports that there is insufficient evidence to suggest that supplementation with betaine and B vitamins reduce the risk of atherosclerosis or that taking these supplements prevents the development or recurrence of heart disease. The AHA does not currently recommend population wide homocysteine screening, and suggests that folic acid, as well as vitamin B6, B12, and betaine requirements be met through diet alone. Individuals at high risk for developing atherosclerosis, however, should be screened for blood levels of homocysteine. If elevated levels are detected, a health care provider may recommend supplementation.

Magnesium. Population based information suggests that people with low magnesium in their diet may be at greater risk for stroke. Some preliminary scientific evidence suggests that magnesium sulfate may be helpful in the treatment of a stroke or transient ischemic attack. More research is needed to know for certain if use of this mineral following a stroke or TIA is helpful. Magnesium may lower blood pressure and potentially interact with some heart medicines.

Omega-3 Fatty Acids. Strong evidence from population-based studies suggests that omega-3 fatty acid intake (primarily from fish) helps protect against stroke caused by plaque buildup and blood clots in the arteries that lead to the brain. In fact, eating at least 2 servings of fish per week can reduce the risk of stroke by as much as 50%. However, people who eat more than 3 grams of omega-3 fatty acids per day (equivalent to 3 servings of fish per day) may be at an increased risk for hemorrhagic stroke, a potentially fatal type of stroke in which an artery in the brain leaks or ruptures. Omega-3 fatty acids may increase the chances of bleeding, especially in those taking anticoagulant medications, such as warfarin (Coumadin) or even aspirin.

The U.S. Food and Drug Administration (FDA) recommends that pregnant women and women of childbearing age, who may become pregnant, limit their consumption of shark, tuna, and swordfish to no more than once a month. These fish have much higher levels of methyl mercury than other commonly consumed fish. Since the fetus may be more susceptible than the mother to the adverse effects of methyl mercury, FDA experts say that it is prudent to minimize the consumption of fish that have higher levels of methyl mercury, like shark, tuna, and swordfish.

Potassium. Although low levels of potassium in the blood may be associated with stroke, taking potassium supplements does not seem to reduce the risk of having a stroke.

Vitamin C. Having low levels of vitamin C contributes to the development of atherosclerosis and other damage to blood vessels and the consequences, such as stroke. Vitamin C supplements may also improve cognitive function if you have suffered from multiple strokes.

Vitamin E. Eating plenty of foods rich in vitamin E, along with other antioxidants like vitamin C, selenium, and carotenoids, reduces your risk for stroke. In addition, low levels of vitamin E in the blood may be associated with risk of dementia (memory impairment) following stroke. Animal studies also suggest that vitamin E supplements, possibly in combination with alpha-lipoic acid, may reduce the amount of brain damaged if taken prior to the actual stroke. Researchers suggest testing this theory in people who are at high risk for stroke. Thus far, however, some large and well-designed studies of people suggest that it is safest and best to obtain this antioxidant via food sources and that supplements do not provide any added benefit.

Others. Additional supplements that require further research but may be useful as part of the treatment or prevention of stroke include:

Coenzyme Q10 -- works as an antioxidant and may reduce damage following a stroke. CO Q10 may interfere with some blood-thinning medicines, such as warfarin (Coumadin) and others.

Selenium -- low levels can worsen atherosclerosis and its consequences. However, it is not known if taking selenium supplements will help.

Herbs

The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, contain active substances that can trigger side effects and interact with other herbs, supplements, or medications. For these reasons, you should take herbs only under the supervision of a health care provider knowledgeable in the field.

Bilberry (Vaccinium myrtillus). A close relative of the cranberry, bilberry fruits contain flavonoid compounds called anthocyanidins. Flavonoids are plant pigments that have excellent antioxidant properties. This means that they scavenge damaging particles in the body known as free radicals and may help prevent a number of long term illnesses, such as heart disease.

Garlic (Allium sativum). Clinical studies suggest that fresh garlic and garlic supplements may prevent blood clots and destroy plaque. Blood clots and plaque block blood flow and contribute to the development of heart attack and stroke. Garlic may also be beneficial for reducing risk factors for heart disease and stroke like high blood pressure, high cholesterol, and diabetes. Homocysteine, similar to cholesterol, may contribute to increasing amounts of blood clots and plaque in blood vessels. If you take aspirin or other blood thinners like warfarin (Coumadin), ACE inhibitors (a class of blood pressure medications), sulfonylureas for diabetes, or statins for high cholesterol, talk to your doctor before using garlic supplements.

Ginkgo (Ginkgo biloba). Gingko may reduce the likelihood of dementia following multiple strokes (often called multi-infarct dementia). The protection from ginkgo may be related to the prevention of platelet adhesion which can help prevent blood clot formation. Most health care providers choose to use medications for this effect rather than herbs. Ginkgo may also decrease the amount of brain damage following a stroke. While animal studies support these possible benefits of ginkgo, more research in people is needed. Also, ginkgo should not be used with the blood thinner warfarin (Coumadin) unless specifically instructed by your health care provider.

Ginseng (Panax ginseng). Asian ginseng may decrease endothelial cell dysfunction. Endothelial cells line the inside of blood vessels. When these cells are disturbed, referred to as dysfunction, it may lead to a heart attack or stroke. The potential for ginseng to quiet down the blood vessels may prove to be protective against these conditions. Much more research is needed. Ginseng may also thin your blood and, therefore, should be used only under the supervision of a doctor if you are taking blood thinning medication warfarin (Coumadin).

Turmeric (Curcuma longa). Early studies suggest that turmeric may prove helpful in preventing heart attack or stroke in one of two ways. First, in animal studies an extract of turmeric lowered cholesterol levels and inhibited the oxidation of LDL ("bad") cholesterol. This is helpful because oxidized LDL deposits in the walls of blood vessels and contributes to the formation of atherosclerotic plaque and other damage to the vessels. Turmeric may also prevent platelet build up along the walls of an injured blood vessel. Platelets collecting at the site of a damaged blood vessel cause blood clots to form and contribute to blockage of the artery as well. Turmeric may also thin your blood and, therefore, should only be used under the supervision of a health care provider, particularly if you are taking blood-thinning medications such as warfarin (Coumadin). Clinical studies of the use of turmeric to prevent or treat stroke in people would be interesting in terms of determining if these mechanisms discovered in animals apply to people at risk for this condition.

Homeopathy

Although an experienced homeopath might prescribe a regimen for treating stroke that includes one of the remedies listed below, the scientific evidence to date does not confirm the value of homeopathy for this purpose.

Acontitum napellus for numbness or paralysis after a cerebral accident

Belladonna for stroke that leaves the person very sensitive to any motion, with vertigo and trembling

Kali bromatum for stroke resulting in restlessness, wringing of the hands or other repeated gestures, insomnia, and night terrors

Many studies have been conducted on the effects of acupuncture during stroke rehabilitation. These studies show that acupuncture reduces hospital stays and improves recovery speed. Acupuncture has been shown to help stroke patients regain motor and cognitive skills and to improve their ability to manage daily functioning. Based on the available data, the National Institutes of Health recommend acupuncture as an alternative or supplemental therapy for stroke rehabilitation. In general, the evidence indicates that acupuncture is most effective when initiated as soon as possible after a stroke occurs, but good results have been found for acupuncture started as late as 6 months following a stroke.

People who have suffered a stroke often have a deficiency of qi in the liver meridian and a relative excess in the gallbladder meridian. In addition to a primary needling treatment on the liver meridian and the supporting kidney meridians, moxibustion (a technique in which the herb mugwort is burned over specific acupuncture points) may be used to enhance therapy. Treatment may also include performing acupuncture on affected limbs. Certain scalp acupuncture techniques that have been developed by Chinese, Korean, and Japanese practitioners also show promise.

Chiropractic

Chiropractors do not treat stroke, and high velocity manipulation of the upper spine is considered inappropriate in individuals who are taking blood-thinning medications or other medications used to reduce the risk of stroke. It should also be noted that chiropractic spinal manipulation of the neck is associated with an exceedingly small risk of causing stroke (reports range from 1 per 400,000 to 1 per 2,000,000).

Traditional Chinese Medicine

In Traditional Chinese Medicine, there are reports of more than 100 substances that have been used to treat stroke. In fact, pharmacologic research of these substances is focused on understanding the ingredients and their mechanisms of action in order to develop new drugs.

Prognosis and Complications

There are many possible complications associated with stroke.

Seizures

Paralysis

Cognitive (thinking) deficits

Speech problems

Emotional difficulties

Daily living problems

Pain

Many people begin to recover from a stroke almost immediately after it has occurred.

The recovery process is most rapid in the first 3 months after a stroke, but improvement will continue for 6 months or a year. Many stroke survivors even report that they slowly continue to regain function for years after their stroke. It is very important not to lose hope.

Broderick J, Connolly S, Feldmann E, et al; American Heart Association/American Stroke Association Stroke Council; American Heart Association/American Stroke Association High Blood Pressure Research Council; Quality of Care and Outcomes in Research Interdisciplinary Working Group. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Circulation. 2007;116(16):e391-413.

Carod-Artal FJ, Egido JA. Quality of life after stroke: the importance of a good recovery. Cerebrovasc Dis. 2009;27 Suppl 1:204-14.